Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats.

Abstract

Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

• Authors: Zhi Wang, Huijuan Zhao, Shuling Peng, Zhiyi Zuo
• Journal: Experimental neurology (Exp Neurol) Vol. 249 Pg. 74-82 (Nov 2013) ISSN: 1090-2430 [Electronic] United States
• PMID: 23994718 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Inflammation Mediators
• Neuroprotective Agents
• Pyrrolidines
• Thiocarbamates
• pyrrolidine dithiocarbamic acid

Topics

• Administration, Intranasal
• Animals
• Animals, Newborn
• Brain (drug effects, metabolism, pathology)
• Dose-Response Relationship, Drug
• Female
• Hypoxia-Ischemia, Brain (metabolism, pathology, prevention & control)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Male
• Neuroprotective Agents (administration & dosage)
• Pyrrolidines (administration & dosage)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Thiocarbamates (administration & dosage)